Persons with DS have broad cognitive impairment and physical characteristics which limit their ability to perform functional tasks of daily living, compared with other people with ID without DS. To date, there have been few, if any, behavioral interventions that have been shown effective in improving cognitive, motor and emotional functioning in adolescents with DS. Exercise is a logical therapy because it has been repeatedly shown to improve cognitive, physical and mental health in typical populations. However, current exercise recommendations for persons with DS vary greatly and results on improvement of motor and cognitive functioning are limited. The limitation of previous voluntary exercise interventions for adolescents with DS, is the voluntary aspect of the exercise. Adolescents with DS, in part due to sedentary behaviors and reduced strength, produce slow movements that may limit their ability to sustain exercise at relatively high rates, which would explain the previous nonsignificant therapeutic benefits of exercise on motor and cognitive functioning in persons with DS. Animal research, and recently research with Parkinson's disease patients, has found promising results using an assisted exercise paradigm, in which the participant is exercised at a rate greater than their voluntary exercise rate, which is key to triggering an endogenous increase in neurotrophic factors that are thought to underlie improved motor and cognitive functioning. Our preliminary data with adolescents with DS revealed improvements in the speed of information processing and manual dexterity, even after one assisted exercise session but not in one voluntary exercise session. The current proposal will allow us to extend these findings to a longer (e.g., 8 wk) intervention session with an assisted exercise group, a voluntary exercise group and a no exercise group and expand our motor, cognitive and health measures. The innovation of our approach is to augment adolescents with DS' voluntary exercise rate via mechanical assistance using a specialized stationary cycle with a motor that is engaged during the Assisted Cycle Therapy. The specific aims are to determine the effects of a long term intervention of assisted and voluntary exercise on motor, cognition, physical and mental health outcomes in adolescents with DS. The hypothesis is that the assisted exercise group will exhibit greater improvements in functional behaviors, manual dexterity, measures of executive function, functional exercise capacity, waist circumference, depression and self efficacy compared to those in the voluntary exercise and no exercise groups. Collectively, data from this project will provide the most complete picture regarding the motor, cognitive, and health outcomes of voluntary and assisted exercise in persons with DS and has the potential to dramatically change the quality of their lives. Our proposed exercise intervention is extremely important because it is predicted to enhance neurogensis, which in turn may improve multiple co-morbid conditions in adolescents with DS. PUBLIC HEALTH RELEVANCE: Animal research, and recently research with Parkinson's disease patients, has found promising results using an assisted exercise paradigm, in which the participant is exercised at a rate greater than their voluntary exercise rate, which is key to triggering an endogenous increase in neurotrophic factors that are thought to underlie improved motor and cognitive functioning. The current proposal will allow us to extend our preliminary single session findings to a longer (e.g., 8 wk) intervention session with an assisted exercise group, a voluntary exercise group and a no exercise group and expand our motor, cognitive and health measures. The innovation of our approach is to augment adolescents with DS' voluntary exercise rate via mechanical assistance using a specialized stationary cycle with a motor that is engaged during the Assisted Cycle Therapy, which is extremely important because it is predicted to enhance neurogensis, which in turn may improve multiple co- morbid conditions in adolescents with DS.